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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Experimental & Clinical Cancer Research 1/2017

E2F8, a direct target of miR-144, promotes papillary thyroid cancer progression via regulating cell cycle

Zeitschrift:
Journal of Experimental & Clinical Cancer Research > Ausgabe 1/2017
Autoren:
Jing Sun, Run Shi, Sha Zhao, Xiaona Li, Shan Lu, Hemei Bu, Xianghua Ma, Chuan Su
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13046-017-0504-6) contains supplementary material, which is available to authorized users.

Abstract

Background

Thyroid cancer is the most common malignancy of endocrine system, and papillary thyroid cancer (PTC) is the most common subtype. E2F8, a novel identified E2F family member, was reported to associate with progression of several human cancers, however, its clinical significance and biological role in PTC remain unknown.

Methods

E2F8 or miR-144 expression profiles in PTC tissues were obtained from The Cancer Genome Atlas (TCGA) datasets, and the correlation of E2F8 expression with clinicopathological features was analyzed in a cohort PTC patients. The effects of E2F8 and miR-144 on proliferation were evaluated both in vitro and in vivo. Luciferase reporter assay was used to determine E2F8 was a direct target of miR-144.

Results

E2F8 was widely upregulated in PTC tissues, and overexpression of E2F8 was correlated with more aggressive clinicopathological features. In contrast, we found that silence of E2F8 significantly suppressed proliferation of PTC cells by inducing G1-phase arrest via downregulating Cyclin D1 (CCND1) both in vitro and in vivo. We also identified miR-144 as a tumor-suppressive microRNA that directly targeted E2F8 to inhibit proliferation of PTC cells in vitro and in vivo. Moreover, miR-144 was widely downregulated in PTC, where its expression correlated inversely with E2F8 expression.

Conclusions

Our results demonstrate a new miR-144/E2F8/CCND1 regulatory axis controlling PTC development, which may offer a potential prognostic and therapeutic strategy.

Trial registration

No applicable.
Zusatzmaterial
Additional file 1: Table S1. A list of 143 genes with highest co-expression correlation (Pearson r value > 0.5) with E2F8 in TCGA PTC dataset. (XLSX 13 kb)
13046_2017_504_MOESM1_ESM.xlsx
Additional file 2: Table S2. Sequences of qRT-PCR primers. (XLSX 9 kb)
13046_2017_504_MOESM2_ESM.xlsx
Literatur
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